Fluvoxamine refractory

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Bogetto, F, Bellino, S., Vaschetto, P., and Ziero, S. (2000) Olanzapine augmentation of fluvoxamine-refractory obsessive-compulsive disorder (OCD) a 12-week open trial. Psychiatry Res 96 91-98. 

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Lu, M. L. et al. (2000). Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients. /. Clin. Psychiatry, 61, 594—9. 

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Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

MAOIs, TCAs, lithium, clomipramine (alone or with topical steroids), fluoxetine, and fluvoxamine may reduce the frequency and intensity of this disorder ( 210, 226, 255, 256, 257, 258, 259, 260 and 261) however, controlled trials are needed to conclusively establish efficacy. Relapse after initial improvement has also been reported, however. Data also indicate that both trichotillomania and OCD may respond to venlafaxine ( 262, 263). For children, such treatments should be reserved for only those with the more severe, refractory forms. 

Since clozapine may be the gold standard and the last resort in the treatment of refractory schizophrenia, the authors of a review aimed to discover whether a trial with clozapine is adequate (15). The results favored the approach of increasing the clozapine plasma concentration in treatment-refractory schizophrenic patients who do not respond to an initial low-to-medium dose. Some patients, especially young male smokers, will need dosages over 900 mg/day, and the addition of low-dose fluvoxamine while closely monitoring clozapine concentrations can help to reduce the large number of tablets required, since fluvoxamine increases the clozapine plasma concentration 2- to 3-fold, maximally 5-fold, and reduces N-desmethylclozapine concentrations the combination can lead to non-linear kinetics of clozapine. 

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